Retinoids, which are important therapeutic compounds for the treatment of dermatological disorders and neoplastic diseases, are also associated with teratogenicity in both humans and experimental species. One of the outstanding questions regarding the mechanisms associated with retinoid exposure is the identification of the metabolites that mediate the teratogenic response (proximate teratogen). Previous studies in our laboratory indicate that 13-cis retinoic acid as well as its 4-oxo metabolite are slowly, but extensively transported to the cynomolgus monkey embryo following a teratogenic dose of 13-cis retinoic acid (2.5 mg/kg/day) during a known sensitive period in early pregnancy (gestational day [GD] 16-31). In contrast, all-trans retinoic acid is eliminated more quickly, resulting in lower levels of this isomer in both maternal plasma and the embryo. These results contrast with those obtained in the mouse model and support the idea that 13-cis retinoic acid and its 4-oxo metabolite may also be proximate teratogens in the nonhuman primate. In order to further explore this hypothesis, studies were carried out in collaboration with F. Hoffmann-La Roche Ltd., Basel, Switzerland, using a nonteratogenic regimen of all-trans retinoic acid (5 mg/kg/day, GD 16-31) in order to examine the possible contribution of this isomer to the embryopathy induced by 13-cis retinoic acid. Results to date indicate that plasma values of all-trans retinoic acid are 2- to 7-fold higher after the nonteratogenic regimen than after dosing with a teratogenic dose of 13-cis retinoic acid. Although these results strengthen the suggestion that the teratogenic effects induced by 13-cis retinoic acid in the macaque are probably due to maternal and embryonic exposure to 13-cis retinoic acid, further evaluation of embryonic levels will be required to definitively answer the question of the proximate teratogen. *KEY*Proximate teratogen, Mechanisms of toxicity, Retinoid embryopathy